Palliative Sedation In Patients With Terminal Illness

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Continuing Education Activity

Palliative sedation is indicated when there is intractable distress in patients who are terminally ill or dying. It is a palliative practice geared toward providing relief from pain, anxiety, agitation in patients who otherwise have a short lifespan. The purpose of palliative sedation is to prevent unnecessary suffering and to favor a smooth transition to death. This activity reviews the role of palliative sedation for terminal patients and highlights the ethical and legal issues with this therapy.

Objectives:

  • Identify the indications for palliative sedation.
  • Describe the associated ethical and legal challenges associated with palliative sedation.
  • Outline the pharmacological agents that can be used to provide palliative sedation.
  • Summarize interprofessional team strategies for improving care coordination and communication to advance the utilization of palliative sedation and improve the quality of life in terminally ill patients.

Introduction

Palliative sedation encompasses a broad range of activities aimed at relieving distress in terminally ill patients. It involves therapy targeted at resolving or alleviating refractory symptoms at the end of life.[1][2][3] The most common refractory symptoms for palliative sedation are delirium, intractable pain, and shortness of breath.[4][5] Despite clear palliative benefits in patients, the use of palliative sedation remains quite controversial.[6][7][8] This is partly due to the lack of consistency in defining "refractory symptoms" and lack of adequate knowledge in patients, family members, and health care workers alike regarding the issue of palliative sedation.[3][9] Additionally, ethical and legal issues surrounding this topic as it appears, at least superficially similar to the process of physician-assisted suicide or euthanasia, discourages physicians from initiating conversations or planning for palliative sedation in patients.[10][11]

Prior studies have demonstrated several communication barriers between clinicians, patients, and surrogates that prevent timely planning for end-of-life issues leading to increased anxiety and frustrations towards the medical team.[12] Other studies have shown variability in the practice of continuation sedation in palliative care of patients.[13][14][15] Furthermore, several misconceptions regarding palliative care issues, including hospice, pain control, and palliative sedation, remain inpatients, and their families.[16][17] This article presents a concise review of indications of palliative sedation, legal/ethical issues associated with its use, common misconceptions, and pharmacological agents used for the purpose.

Indications

There is no universal definition for refractory symptoms; thus, it is up to the clinician and the hospital staff's discretion to determine if certain intractable symptoms would warrant the initiation of palliative sedation. However, in general, the following is considered to fit the criteria for palliative sedation:[9][18]

  • The patient considered a candidate for palliative sedation must have a terminal illness where the prognosis is guarded, and death is almost certain. 
  • The patient's clinical presentation must be such that traditional or conventional therapies are incapable of providing relief despite maximal doses, e.g., terminally ill patients with shortness of breath who are already on high flow oxygen via nasal cannula might benefit from the addition of morphine to relieve respiratory distress. 
  • Alternatively, a scenario can exist when conventional therapies are associated with potential adverse outcomes in patients at high doses or frequent administration of agents and thus warranting the use of palliative sedation, e.g., use of frequent and high doses of Ondansetron to relieve nausea and vomiting can be associated with QTc prolongation and cardiac arrhythmias. Using sedating agents such as benzodiazepine (Midazolam) might be a suitable alternative that can relieve nausea and avoid the risk of cardiac arrhythmias. 
  • Additionally, palliative sedation can be considered if traditional therapies cannot provide relief of symptoms in a timely manner, e.g., using intravenous or intramuscular antipsychotics in acutely delirious patients with a terminal illness offers quicker results compared to standard re-orientation techniques in patients. 
  • Well-documented goals of care discussion with the patient or surrogates must be present to outline the plan of care and potential risks of using palliative sedation.

Ethical and Legal Issues [11][19][20][21]

Although there has been a well-demonstrated benefit of better symptom control in patients with a terminal illness, the topic of providing palliative sedation continues to garner some controversy. Most clinicians and organizations' chief concern from administering palliative sedation in patients is that it may inadvertently hasten or quickening someone's demise. Due to this concern, the practice of palliative sedation is still compared with physician-assisted suicide and euthanasia. Below, we will briefly describe the fundamental concept and differences between these therapies in terminally ill patients. 

Euthanasia

Euthanasia constitutes the process by which a third party (health care worker) who is taking care of the patient intentionally uses medications to terminate a patient’s life to end their pain and suffering. It can either be done with the patient’s consent (voluntary euthanasia) or done independently by the health care providers (involuntary euthanasia). The practice of involuntary euthanasia is illegal in all countries. Netherlands and Belgium are currently the only two that allow health care workers to participate in voluntary euthanasia.[19][22]

Physician-Assisted Suicide

Physician-assisted suicide (PAS) is the process by which a physician acts as a facilitator for a patient to hasten death by providing lethal doses of prescription medication. It differs from euthanasia in that the health care worker assumes a passive role of supervision, and the actual administration of medication that leads to death has to be done by the patients on their own.[23]

In the United States, PAS is legal in California, Colorado, District of Columbia, Hawaii, Montana, Maine, New Jersey, Oregon, Vermont, and Washington. In these states, “death with dignity” statutes ensure that mentally competent adult state residents who have a terminal illness with a confirmed prognosis of having 6 or fewer can voluntarily request a prescription for medication that hasten death. Other countries where physician-assisted suicide is legal are Canada, Belgium, the Netherlands, Luxembourg, and Switzerland.[24]

Differentiating Palliative Sedation from Euthanasia and Physician-assisted Suicide

Palliative sedation as a practice differs from euthanasia and physician-assisted suicide on two fronts: intention and the desired outcome. Palliative sedation intends to relieve refractory symptoms in dying patients, whereas the intention of physician-assisted suicide and euthanasia is the terminating patient's life. Similarly, the desired outcome in palliative sedation is to achieve a level of sedation in patients that control their symptoms. Whereas, in physician-assisted suicide and euthanasia, the desired outcome is always the death of the patient. Although some health care workers still raise ethical concerns regarding its use, palliative sedation is legal in all countries, including the United States. 

Preparation

Timing of Palliative Sedation

Determining the most appropriate time to initiate palliative sedation is often a challenging process.[9] Firstly, there are inconsistencies in defining what to label as “refractory symptoms” due to the lack of consensus among clinicians. Secondly, as PS is usually reserved at the end of life of terminally ill patients, determining the prognosis of the disease is an important step in planning for palliative sedation. Prior literature has demonstrated that health care workers are not always reliable when it comes to providing an accurate prognosis of diseases. Thus, labeling a disease as “terminal” and without cure becomes a difficult task for most clinicians.[25][26]

Understanding Proportional Treatment and the Doctrine of “Double Effect” [27][28]

The goal of palliative sedation is to relieve intractable symptoms and not to keep the patient unresponsive. Thus the concept of proportional treatment must be understood while using palliative sedation. Medications such as benzodiazepines, opiates, and antipsychotics are often used to alleviate patients' respiratory distress, agitation, and anxiety and cause sedation. However, it should be noted that the dose and frequency with which these medications should be used should be titrated and always be proportional to the desired clinical benefit. There are certain extreme cases when a patient has to be given a high dose of sedatives; keeping them obtunded is the only way to alleviate their symptoms, e.g., extreme agitation or seizures. However, in most instances, continuous sedation aims to manage intractable symptoms and observe for an adequate response, not merely to keep the patient sedated.

An additional ethical concept that needs to be understood regarding the use of palliative sedation is the doctrine of “double effect.” This doctrine originated from Thomas Aquinas in the 13th century, and it parallels the principles of beneficence and non-maleficence.

This doctrine asserts the follows:

“An action in the pursuit of a good outcome is acceptable, even if it achieved through means with an unintended but foreseeable negative outcome if that negative outcome is outweighed by the good outcome.”

Some recent studies have shown that palliative sedation is safe in terminally ill patients is not associated with an increased risk of death. However, it is important to highlight the use of potential risks of excess sedation. Palliative sedation can be associated with an increased risk of aspiration, respiratory depression, and worsening agitation due to delirium. These adverse outcomes are unintended effects of therapy and not the primary intended outcome in palliative sedation. Thus, as per the doctrine of “double effect,” as long as the patient, family, and physicians are aware of the potential adverse effects coupled with palliative sedation, it can be administered without any hesitation.

Initiating Goals of Care Discussion with Patients, Family Members, or Surrogates

Clinicians and health care workers must identify terminally ill patients with poor prognosis and refractory symptoms who are likely to benefit from palliative sedation. Prior studies have demonstrated several communication barriers and misconceptions in both physicians and patients/family members regarding end of life issues.[14][15] There is ample evidence that shows that there is room for improvement in residents, fellows, and fellows alike when it comes to discussing issues such as reviewing the code status of patients, conveying poor prognosis of the disease, conversion to hospice, and palliative sedation.[16][17] Due to a lack of consensus regarding the definition of palliative sedation and its indications, there are often misconceptions in patients and family members regarding the use of palliative sedation.[16][17] Given its close resemblance to euthanasia and physician-assisted suicide, every attempt must be made to delineate the patient's/family's wishes and manage expectations properly. Having a goal of discussing involving the physician team, patient, family member (or surrogates), palliative care physician, and social workers where once can address the prognosis of the disease, define certain symptoms that have not abated with the use of standard therapy is an important step to initiate a discussion regarding palliative sedation.  The pros and cons of palliative sedation should be explained during this meeting. Potential adverse effects such as the risk of inadvertently hastening death, aspiration, excess sedation must be addressed. 

Discussing Ongoing Care and Obtaining Consent

After a thorough goals-of-care discussion, written or verbal consent must be documented from the patient regarding their willingness to initiate palliative sedation. For patients who cannot communicate their wishes due to a decreased level of consciousness or nonverbal state, we must follow the patient's advance directives, or if there is no advance directive, consent must be obtained from a legally recognized proxy. Patients and families should be assured that being started on palliative sedation does not imply that any ongoing medical or nursing care that has been beneficial to the patient will be withdrawn by default. In fact, detailed goals of care discussion should address what therapies would be added or continued for the patient's care and which can be discontinued. For example, there should be a detailed discussion regarding issues such as feeding and artificial nutrition in terminally ill patients. Clinicians should clearly explain the prognosis and life expectancy and discuss with patients/family members whether it is prudent to continue feeding tubes and nutrition (e.g., the life expectancy of weeks to months where feeding tubes might help in providing hydration and nutrition) or to discontinue it entirely to limit patient distress (life expectancy of hours to days).

Technique

Pharmacology

The following are the common pharmacological agents that can be used in palliative sedation.[29][30][31][32] 

Drug class

Mechanism of action

Indication

Side effects

 

Benzodiazepines

 

e.g. Lorazepam, Midazolam

GABA agonist with CNS depression.

 

Agitated delirium, anxiety.

 

Can cause worsening of confusion and agitation when administered frequently. When administered with other agents such as opiates, it can cause respiratory depression.

 

Antipsychotics (first generation)

e.g., haloperidol, chlorpromazine.

 

 

 

Dopamine D2 blockade in haloperidol and, additionally, 5HT, H, alpha, alpha, and a muscarinic antagonist in chlorpromazine.

Agitated delirium.

 

 

 

Anticholinergic effects, orthostatic hypotension (which can be severe) with rapid IV administration, akathisia, acute dystonic reactions, seizures, and cardiotoxicity associated with QT prolongation.

 

 

Propofol

 

 

GABA agonist and potentially by inhibition of glutamate

 

For agitated delirium in patients with poor response to antipsychotics and benzodiazepines.

Hypotension, thrombophlebitis, propofol infusion syndrome.

 

 

Barbiturates

 

 

GABA agonist and inhibition of glutamate.

 

For agitated delirium in patients with poor response to antipsychotics and benzodiazepines.

Hemodynamic instability (low blood pressure and heart rate), nausea, vomiting. Enzyme induction and resultant decreased efficacy of other drugs.

 

Opiates

e.g., morphine, fentanyl, oxycodone

 

Binds to opioid receptors (e.g., mu) in the CNS and causes CNS depression.

 

 

For pain relief and respiratory distress.

 

It can lead to respiratory depression.

Respite Sedation vs. Continuous Sedation

Respite sedation refers to the temporary use of sedative agents to relieve symptoms such as pain, nausea, agitation. These symptoms may or may not be refractory. Patients are typically started on sedative agents for a brief, predetermined period (e.g., 24 to 48 hours) with frequent reassessment. The dose of the sedating agent is then decreased till the patient is fully conscious after the predetermined period, e.g., using propofol for sedation and analgesia in a patient presenting with an acutely dislocated shoulder while planning for reduction of the joint.

Most patients with a terminal illness and refractory pain who have shown poor response to conventional therapy are placed on continuous sedation. As the name suggests, with this form of sedation, no attempt is made to wean the sedative medication off, and it is typically continued till the patient's demise. 

Complications

The use of palliative sedation continues to be a controversial topic, given that its use can potentially hasten death. As such, the pros and cons of palliative sedation should be clearly outlined to the patient/family to manage expectations. Excess sedation can theoretically cause an increased risk of aspiration pneumonia and respiratory suppression. However, contrary to this belief, recent studies have demonstrated that palliative sedation can, in fact, be safely administered without any disproportionate increase in the incidence of aspiration pneumonia or respiratory failure.[33] Additionally, other studies have demonstrated that the time till death is not significantly shortened in patients receiving palliative sedation compared to patients receiving standard or alternative therapy.[34][35]

Clinical Significance

Identifying terminally ill patients with refractory symptoms and timely initiation of goals-of-care discussion are paramount to patient's care. It will not only ensure that patient's wishes are honored but also withhold the use of any redundant therapy or invasive procedure that is unlikely to improve the patient's symptoms or delay disease progression. Prior studies have demonstrated that palliative care has enormous benefits in patients beyond just pain control. These studies reveal the provision of interprofessional care and family meetings enhances the bond between the patient/family, caregiver and relieves stress, anxiety frustration.[36][37]

Enhancing Healthcare Team Outcomes

Providing palliative care requires an interprofessional team approach. It includes managing a broad range of refractory symptoms, including shortness of breath, agitation, delirium, and pain. In the current context, most healthcare institutions have a palliative management team that assesses patients for their palliative needs. The team usually consists of a physician, nurse, pharmacist, pain specialist, a religious figure, and a member of the ethics committee. Palliative care should be individualized for each patient based on goals of care discussions with the patient and family. Nurses and the pharmacist are vital team members as they closely monitor the patient for adverse effects and effectiveness of the sedative medications. In addition to pharmacological methods to relieve pain, there are also several non-pharmacological methods available. Some of these nonpharmacological methods are radiation therapy, radiofrequency ablation, heat, ice, or coolant sprays and may warrant the inclusion of other specialties such as pain medicine, radiation oncology, etc. 



(Click Image to Enlarge)
Palliative Sedation
Palliative Sedation
Contributed by Mohammed Al-Dhahir, MD
Article Details

Article Author

Poonam Bhyan

Article Author

Michael Pesce

Article Author

Utsav Shrestha

Article Editor:

Amandeep Goyal

Updated:

7/25/2021 9:51:50 PM

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